Journal of Proteomics & Bioinformatics
Open Access
ISSN: 0974-276X
ISSN: 0974-276X
Department of Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Research Article
ARDiTox: Platform for the Prediction of T-Cell Receptors (TCRs) Potential Off-Target Binding
Author(s): Victor Murcia Pienkowski*, Tamara Boschert, Piotr Skoczylas, Anna Sanecka-Duin, Maciej Jasinski, Bartlomiej Krol-Jozaga, Giovanni Mazzocco, Slawomir Stachura, Lukas Bunse, Jan Kaczmarczyk, Edward W. Green and Agnieszka Blum
Cellular immunotherapies, such as those utilizing T lymphocytes expressing native or engineered T-cell Receptors (TCRs), have already demonstrated therapeutic efficacy. However, some high-affinity TCRs have also proved to be fatal due to off-target immunotoxicity. This process occurs when the immune system acts against epitopes found on both tumor cells and healthy tissues. Moreover, some TCRs can be cross-reactive to epitopes with highly dissimilar sequences. To address this issue, we developed ARDitox, a novel in silico method based on computational immunology and Artificial Intelligence (AI), for predicting and analyzing potential off-target toxicities. We tested the performance of ARDitox in silico on 4 different epitopes found in the literature where TCRs were used to target cancer-related antigens as well as on a set of TCR targeting a viral epitope... View More»
DOI:
10.35248/0974-276X.23.16.651